GABA-modulin, an endogenous membrane protein, which inhibits non competitively 3H-GABA binding to synaptic plasma membranes, has been isolated and purified to homogeneity using acidic extraction followed by Sephadex column purification and HPLC. GABA-modulin is a synaptosomal peptide of 16,000 MW which inhibits the binding of 3H-GABA and the GABA-induced stimulation of 3H-diazepam binding to synaptic membranes. The GABA-modulin molecule contains an abundance of hydrophilic residues (especially basic residues), and no cystein or GABA. End group analyses of GABA-modulin indicated that the carboxy terminus if free, while the N-terminus is blocked. GABA-modulin can be phosphorylated by cAMP and Ca++ calmodulin dependent protein kinase. Phosphorylation of GABA-modulin by cAMP resulted in the lost of inhibition on GABA receptors. The role of GABA-modulin in the control of GABA receptor system function is presently being investigated.